Ethanol Exposure Decreases Glutamate Uptake in the Nucleus Accumbens


Reprint requests: Roberto I. Melendez, PhD, Medical University of South Carolina, Department of Physiology and Neuroscience, 173 Ashley Avenue, Suite 403 BSB, Charleston, SC 29425; Fax: 843-792-4423; E-mail:



An increased level of extracellular glutamate is a key neurochemical feature associated with ethanol exposure and withdrawal.


In the current study, extracellular levels of glutamate and glutamate transport in the nucleus accumbens were assayed 24 hr after repeated ethanol exposure (1 g/kg ip daily for 7 days) with use of in vivo no-net-flux microdialysis and in vitro 3Hglutamate uptake, respectively.


Microdialysis revealed higher extracellular glutamate concentrations in the nucleus accumbens of rats that were given ethanol. The increase in basal extracellular glutamate levels was accounted for in part by a decrease in the in vivo probe recovery of glutamate. Moreover, an in vitro accumbens slice preparation measuring 3Hglutamate uptake revealed that Na+-dependent 3Hglutamate uptake was significantly reduced 24 hr after 7 days of repeated ethanol exposure. The ethanol-induced deficit in glutamate uptake was not associated with decreased total tissue levels of the transporters GLAST or GLT1. The in vivo and in vitro ethanol-induced changes in glutamate levels and uptake returned to control levels 14 days after discontinuing 7 days of repeated ethanol exposure.


These results suggest that the previously reported increases in extracellular glutamate induced by ethanol exposure may be due in part to deficits in glutamate transport.